Sara Pedron Haba (RBTE) and Brendan Harley (RBTE leader/EIRH), both professors of Chemical & Biomolecular Engineering, are making strides in the long march to better targeting and treatment of glioblastoma (GBM). In a paper published in Advanced Therapeutics, Pedron Haba, Harley, and co-author Roddel Remy report findings with import for our understanding of GBM cell proliferation.

With the critical support from the Cancer Center at Illinois' Tumor Engineering and Phenotyping (TEP) laboratory, the team used tissue engineering to recreate the 3D tumor microenvironment in vitro and analyze changes in an array of patient-derived GBM cells. The study uncovered data showing an important role that hyaluronic acid (or hyaluronan) plays in GBM cell growth.

“This study was a continuation of earlier GBM research projects looking at biomaterial-based systems to understand how cancer cells interact with the tumor microenvironment and respond to different therapeutic strategies,” said Pedron Haba. “We wanted to dive deeper into our understanding of the metabolic pathways in the context of the tumor microenvironment that are associated treatment resistance.”

This question led Pedron Haba’s team to collaborate with the TEP, which provided critical research assistance to expand the study’s capabilities. “Normally, the TEP’s Seahorse Analyzer is used for 2D cell cultures, but with Sara’s study we were able to optimize the Seahorse for 3D cell cultures to monitor the metabolic pathway changes in the live GBM cells,” said TEP Manager Hui Xu. “We don’t run standard protocols at TEP, because each researcher’s investigation is unique. We want to understand the study and adjust our approaches to maximize their research impact.”

About Glioblastoma
The GBM tumor microenvironment is a highly complex and interconnected ecosystem. The interactions between glioma stem cells, extracellular matrix (ECM), immune cells, neural networks, and vascular system have proven to be essential in cancer progression and therapeutic response. An expanded understanding of the GBM tumor microenvironment could provide researchers with additional strategic targets to help GBM patients with better therapeutic approaches and outcomes. “In light of this great need in GBM research, for this study we focused on developing hydrogel models to investigate the role of hyaluronan (HA)-cell interactions in the metabolic pathways,” said Pedron Haba.

HA is the major player in the brain extracellular matrix and a critical component of the tumor microenvironment. Due to its influence in biological signals, HA has become a primary focus in the design of biomaterial platforms as disease models. The fabrication of controlled microenvironments provided by 3D models helps to reveal the role of HA signaling in GBM tumors.

With the TEP’s research support, Pedron Haba’s team found that HA fragments can enhance tumor metabolism and growth through receptor-signaling dependent pathways and receptor-signaling independent pathways. This work emphasizes the potential of these preclinical models to predict and accelerate cancer treatments.

“This project highlights the great asset that TEP is for cancer research on our campus. It was helpful to be able to work with Hui to optimize the TEP’s equipment for our study, which shows the benefit that the TEP’s trained technicians provide to accelerate and increase the impact our research,” said Pedron Haba.

Conclusion
This study demonstrates that low molecular weight HA enables some glioblastoma tumors with the capacity to recuperate from the effects of targeted inhibitors, and that inhibitors of hyaluronan degradation can sensitize tumor cells by selectively inducing the accumulation of hyaluronan. This preclinical tool can provide data to predict the outcome of more precise GBM treatments and discover new biomarkers

In addition to this research direction, Pedron Haba will continue her larger GBM investigation of the relationship between neural networks and cancer cells. Learn more about that project here.

The paper “Targeting Glioblastoma Tumor Hyaluronan to Enhance Therapeutic Interventions that Regulate Metabolic Cell Properties” is available online: doi.org/10.1002/adtp.202400041